The overall objectives of the proposed studies are to evaluate factors which regulate megakaryocytopoiesis and platelet production. Of interest are feed-back regulation by circulating platelets, the relationship of megakaryocytes to pluripotential stem cells, and the role of the hematopoietic microenvironment in regulating megakaryocytopoiesis. Studies are being done in conventional, S1/S1d and W/Wv mice, utilizing perturbations of circulating platelet levels, cell and tissue transplantation, irradiation, and cell culture. BIBLIOGRAPHIC REFERENCES: Ebbe, S., Howard, D., Phalen, E., and Stohlman, F., Jr.: Effects of vincristine on normal and stimulated megakaryocytopoiesis in the rat. Brit. J. Haemat. 29: 593-603, 1975. Ebbe, S., Phalen, E., and Ryan, M.K.: Non-microenvironmental regulation of megakaryocytes in S1/S1d mice. (abstract). Am. Soc. of Hemat., 1975, page 192 of program.